There are two large chains for the brine shrimp Na,K-ATPase which have different kinetic properties (different phosphorylation by ATP and different affinity for ouabain binding. We have called these two chains alpha 1 and alpha 2. Alpha 2 reaches its maximum at about 12 hrs. of development and then disappears by about 48 hrs. The data best fit the concept of polymorphism during development. Testing this hypothesis is continuing. We have returned to the "phospholipid effect" which we discovered in 1952 (Hokin and Hokin, J. Biol. Chem. 203, 967 (1953)). The phospholipid effect was previously known to involve increased turnover of phosphatidyl inositol (PI) and phosphatidic acid (PA) as well as a breakdown of PI and a net synthesis of PA. We have found that during breakdown of PI, in response to secretogogues, arachidonic acid is released and is converted to prostaglandin E 2 (PGE2). With the use of aspirin-like drugs, we have been able to show if this conversion is blocked so that no PGE2 forms and secretion is blocked, even though PI breakdown still occurs. Work is in progress to see what the immediate breakdown product of PI is (lyso PI?, diglyceride?). We are also trying to find out if Ca is related to PGE2 in stimulus-secretion coupling. Insulin secretion is stimulated by aspirin. We are isolating islet cells and studying the PI-PG axis during stimulation of insulin secretion and the effects of aspirin-like drugs on secretion and prostaglandin formation. Brain cortex slices show a phospholipid effect very similar to that of the acinar pancreas in response to acetylcholine (ACh). We are attempting to see if prostaglandins are also released here during the phospholipid effect.